Surgical techniques for optimal lens management of posterior segment metallic intraocular foreign body removal: a case series.

PURPOSE: We describe three different approaches for lens management in cases of metallic IOFBs involving the posterior segment. METHODS: All consecutive posterior segment metallic IOFB cases from 2012 to 2023 at a single institution were included in this retrospective case series. Surgical outcomes and surgical videos are presented. RESULTS: A total of 25 metallic IOFB cases were included. In 9 cases, there was no significant lens involvement, therefore not requiring lens extraction at the time of IOFB removal. In 8 cases with traumatic cataract, lens extraction sparing the anterior lens capsule was performed with IOFB removal. In 8 cases, both lens extraction and lens capsule removal were required at the time of IOFB removal. CONCLUSION: We demonstrate our algorithm to capsular management in patients who present with IOFB with good visual outcomes in follow-up.

Weighted Breaths: Exploring Biologic and Non-Biologic Therapies for Co-Existing Asthma and Obesity.

PURPOSE OF REVIEW: To discuss the effectiveness of biologics, some of which comprise the newest class of asthma controller medications, and non-biologics in the treatment of asthma co-existing with obesity. RECENT FINDINGS: Our review of recent preliminary and published data from clinical trials revealed that obese asthmatics respond favorably to dupilumab, mepolizumab, omalizumab, and tezepelumab, which are biologics currently indicated as add-on maintenance therapy for severe asthma. Furthermore, clinical trials are ongoing to assess the efficacy of non-biologics in the treatment of obese asthma, including a glucagon-like peptide-1 receptor agonist, a Janus kinase inhibitor, and probiotics. Although many biologics presently indicated as add-on maintenance therapy for severe asthma exhibit efficacy in obese asthmatics, other phenotypes of asthma co-existing with obesity may be refractory to these medications. Thus, to improve quality of life and asthma control, it is imperative to identify therapeutic options for all existing phenotypes of obese asthma.

What are participant beliefs regarding physical therapy led treatment? A qualitative study of people living with femoroacetabular impingement syndrome.

BACKGROUND: Physical therapist-led treatment programs are recommended for patients with femoroacetabular impingement (FAI) syndrome. Views of people with FAI syndrome regarding such interventions are currently unknown, including perceptions of potential barriers and facilitators to participation and adherence to exercise programs. OBJECTIVES: To explore participant perceptions of physical therapist-led programs for FAI syndrome, including barriers and facilitators for accessing physical therapy, and adhering to a rehabilitation program. METHODS: Our qualitative study used semi-structured interviews to explore the perceptions of patients with FAI syndrome undertaking physical therapy-led treatment, where treatment was ceased due to Coronavirus Disease 2019 (COVID-19). The interview topic guide was informed by the Theoretical Domain Framework. Interviews were transcribed verbatim and data categories were developed using inductive thematic analysis. Themes were discussed between researchers until consensus was reached. RESULTS: Fourteen participants (mean age: 30 years) with a range of physical activity backgrounds undertook interviews. We identified four key themes, 1) Patients believed their hip pain was caused by structural damage worsened through exercise; 2) Barriers and facilitators on the feasibility of physical therapist-led programs; 3) Participants held beliefs regarding the importance of adjunct treatments to exercise; and 4) Impact of FAI syndrome on physical activity participation. CONCLUSION: People with FAI syndrome believe they have structural damage which leads to their hip pain and are often afraid to exercise due to fear of causing more damage to their hip. Our findings suggest that people with FAI syndrome want clear education about exercise, imaging, and expectations of cost and duration of treatment.

Will you get what you want? Treatment goals and expectations of patients with femoroacetabular impingement syndrome regarding physiotherapist-led treatment.

OBJECTIVE: To (i) investigate the goals and expectations of participants enrolled in a clinical trial of physiotherapist-led treatment for femoroacetabular impingement (FAI) syndrome and (ii) explore associations between their expectations and self-reported hip burden and kinesiophobia. METHODS: Data from 150 participants with FAI syndrome who participated in a clinical trial were analysed. Participants described their most important treatment goal and the expectation of achieving this goal throughout physiotherapy treatment. The International Hip Outcome Tool (iHOT-33) subscales were used to assess self-reported hip burden. The Tampa Scale for Kinesiophobia was used to assess kinesiophobia. Participants goals were qualitatively analysed using content analysis. Linear regression was used to explore associations between patient expectations and iHOT and Tampa Scale for Kinesiophobia scores. RESULTS: Participants with FAI syndrome reported goals relating to exercise (52%), improving activities of daily living quality (23%), improving physical function (15%), and reducing pain (10%). Negative expectations regarding physiotherapist-led treatment were reported by 68% of participants. Those with negative expectations reported worse scores for the iHOT-Total score (mean difference = 12 points, 95%CI = [4 to 19]), and iHOT-Symptoms (14 points, [7 to 21]) and iHOT-Social (11 points, [2 to 21]) subscales compared to those with positive expectations. Treatment expectations were not associated with iHOT-Sport, iHOT-Job, and Tampa Scale for Kinesiophobia scores (p > 0.05). CONCLUSION: Patients with FAI syndrome had a generally negative expectation of physiotherapist-led treatment. There was a mismatch between patients' goals and current treatment approaches. Participants with FAI syndrome and negative expectations reported worse quality of life, symptoms, and social concerns than those with positive expectations.

Brain-wide arousal signals are segregated from movement planning in the superior colliculus.

The superior colliculus (SC) is traditionally considered a brain region that functions as an interface between processing visual inputs and generating eye movement outputs. Although its role as a primary reflex center is thought to be conserved across vertebrate species, evidence suggests that the SC has evolved to support higher-order cognitive functions including spatial attention. When it comes to oculomotor areas such as the SC, it is critical that high precision fixation and eye movements are maintained even in the presence of signals related to ongoing changes in cognition and brain state, both of which have the potential to interfere with eye position encoding and movement generation. In this study, we recorded spiking responses of neuronal populations in the SC while monkeys performed a memory-guided saccade task and found that the activity of some of the neurons fluctuated over tens of minutes. By leveraging the statistical power afforded by high-dimensional neuronal recordings, we were able to identify a low-dimensional pattern of activity that was correlated with the subjects' arousal levels. Importantly, we found that the spiking responses of deep-layer SC neurons were less correlated with this brain-wide arousal signal, and that neural activity associated with changes in pupil size and saccade tuning did not overlap in population activity space with movement initiation signals. Taken together, these findings provide a framework for understanding how signals related to cognition and arousal can be embedded in the population activity of oculomotor structures without compromising the fidelity of the motor output.

Inconsequential role for chemerin-like receptor 1 in the manifestation of ozone-induced lung pathophysiology in male mice.

We executed this study to determine if chemerin-like receptor 1 (CMKLR1), a Gi/o protein-coupled receptor expressed by leukocytes and non-leukocytes, contributes to the development of phenotypic features of non-atopic asthma, including airway hyperresponsiveness (AHR) to acetyl-ß-methylcholine chloride, lung hyperpermeability, airway epithelial cell desquamation, and lung inflammation. Accordingly, we quantified sequelae of non-atopic asthma in wild-type mice and mice incapable of expressing CMKLR1 (CMKLR1-deficient mice) following cessation of acute inhalation exposure to either filtered room air (air) or ozone (O3), a criteria pollutant and non-atopic asthma stimulus. Following exposure to air, lung elastic recoil and airway responsiveness were greater while the quantity of adiponectin, a multi-functional adipocytokine, in bronchoalveolar lavage (BAL) fluid was lower in CMKLR1-deficient as compared to wild-type mice. Regardless of genotype, exposure to O3 caused AHR, lung hyperpermeability, airway epithelial cell desquamation, and lung inflammation. Nevertheless, except for minimal genotype-related effects on lung hyperpermeability and BAL adiponectin, we observed no other genotype-related differences following O3 exposure. In summary, we demonstrate that CMKLR1 limits the severity of innate airway responsiveness and lung elastic recoil but has a nominal effect on lung pathophysiology induced by acute exposure to O3.

Variation and covariation of external shape and cross-sectional geometry in the human metacarpus.

OBJECTIVES: Analyses of external bone shape using geometric morphometrics (GM) and cross-sectional geometry (CSG) are frequently employed to investigate bone structural variation and reconstruct activity in the past. However, the association between these methods has not been thoroughly investigated. Here, we analyze whole bone shape and CSG variation of metacarpals 1-5 and test covariation between them. MATERIALS AND METHODS: We analyzed external metacarpal shape using GM and CSG of the diaphysis at three locations in metacarpals 1-5. The study sample includes three modern human groups: crew from the shipwrecked Mary Rose (n = 35 metacarpals), a Pre-industrial group (n = 50), and a Post-industrial group (n = 31). We tested group differences in metacarpal shape and CSG, as well as correlations between these two aspects of metacarpal bone structure. RESULTS: GM analysis demonstrated metacarpus external shape variation is predominately related to changes in diaphyseal width and articular surface size. Differences in external shape were found between the non-pollical metacarpals of the Mary Rose and Pre-industrial groups and between the third metacarpals of the Pre- and Post-industrial groups. CSG results suggest the Mary Rose and Post-industrial groups have stronger metacarpals than the Pre-industrial group. Correlating CSG and external shape showed significant relationships between increasing external robusticity and biomechanical strength across non-pollical metacarpals (r: 0.815-0.535; p ≤ 0.05). DISCUSSION: Differences in metacarpal cortical structure and external shape between human groups suggest differences in the type and frequency of manual activities. Combining these results with studies of entheses and kinematics of the hand will improve reconstructions of manual behavior in the past.

Identification of LY3522348: A Highly Selective and Orally Efficacious Ketohexokinase Inhibitor.

The identification of clinical candidate LY3522348 (compound 23) is described. LY3522348 is a highly selective, oral dual inhibitor of human ketohexokinase isoforms C and A (hKHK-C, hKHK-A). Optimization began with highly efficient (S)-2-(2-methylazetidin-1-yl)-6-(1H-pyrazol-4-yl)-4-(trifluoromethyl)nicotinonitrile (3). Efforts focused on developing absorption, distribution, metabolism, potency, and in vitro safety profiles to support oral QD dosing in patients. Structure-based design leveraged vectors for substitution of the pyrazole ring, which provided an opportunity to interact with several different proximal amino acid residues in the protein. LY3522348 displayed a robust pharmacodynamic response in a mouse model of fructose metabolism and was advanced into clinical trials.

Exploring the link between coffee matrix microstructure and flow properties using combined X-ray microtomography and smoothed particle hydrodynamics simulations.

Coffee extraction involves many complex physical and transport processes extremely difficult to model. Among the many factors that will affect the final quality of coffee, the microstructure of the coffee matrix is one of the most critical ones. In this article, we use X-ray micro-computed (microCT) technique to capture the microscopic details of coffee matrices at particle-level and perform fluid dynamics simulation based on the smoothed particle hydrodynamics method (SPH) with the 3D reconstructured data. Information like flow permeability and tortuosity of the matrices can be therefore obtained from our simulation. We found that inertial effects can be quite significant at the normal pressure gradient conditions typical for espresso brewing, and can provide an explanation for the inconsistency of permeability measurements seen in the literature. Several types of coffee powder are further examined, revealing their distinct microscopic details and resulting flow features. By comparing the microCT images of pre- and post-extraction coffee matrices, it is found that a decreasing porosity profile (from the bottom-outlet to the top-inlet) always develops after extraction. This counterintuitive phenomenon can be explained using a pressure-dependent erosion model proposed in our prior work. Our results reveal not only some important hydrodynamic mechanisms of coffee extraction, but also show that microCT scan can provide useful microscopic details for coffee extraction modelling. MicroCT scan establishes the basis for a data-driven numerical framework to explore the link between coffee powder microstructure and extraction dynamics, which is the prerequisite to study the time evolution of both volatile and non-volatile organic compounds and then the flavour profile of coffee brews.

Building Career Paths for Ph.D., Basic and Translational Scientists in Clinical Departments in the United States: An Official American Thoracic Society Workshop Report.

Rationale: To identify barriers and opportunities for Ph.D., basic and translational scientists to be fully integrated into clinical units. Objectives: In 2022, an ad hoc committee of the American Thoracic Society developed a project proposal and workshop to identify opportunities and barriers for scientists who do not practice medicine to develop successful careers and achieve tenure-track faculty positions in clinical departments and divisions within academic medical centers (AMCs) in the United States. Methods: This document focuses on results from a survey of adult and pediatric pulmonary, critical care, and sleep medicine division chiefs as well as a survey of workshop participants, including faculty in departmental and school leadership roles in both basic science and clinical units within U.S. AMCs. Results: We conclude that full integration of non-clinically practicing basic and translational scientists into the clinical units, in addition to their traditional placements in basic science units, best serves the tripartite mission of AMCs to provide care, perform research, and educate the next generation. Evidence suggests clinical units do employ Ph.D. scientists in large numbers, but these faculty are often hired into non-tenure track positions, which do not provide the salary support, start-up funds, research independence, or space often associated with hiring in basic science units within the same institution. These barriers to success of Ph.D. faculty in clinical units are largely financial. Conclusions: Our recommendation is for AMCs to consider and explore some of our proposed strategies to accomplish the goal of integrating basic and translational scientists into clinical units in a meaningful way.

Burden of disease attributable to unsafe drinking water, sanitation, and hygiene in domestic settings: a global analysis for selected adverse health outcomes.

BACKGROUND: Assessments of disease burden are important to inform national, regional, and global strategies and to guide investment. We aimed to estimate the drinking water, sanitation, and hygiene (WASH)-attributable burden of disease for diarrhoea, acute respiratory infections, undernutrition, and soil-transmitted helminthiasis, using the WASH service levels used to monitor the UN Sustainable Development Goals (SDGs) as counterfactual minimum risk-exposure levels. METHODS: We assessed the WASH-attributable disease burden of the four health outcomes overall and disaggregated by region, age, and sex for the year 2019. We calculated WASH-attributable fractions of diarrhoea and acute respiratory infections by country using modelled WASH exposures and exposure-response relationships from two updated meta-analyses. We used the WHO and UNICEF Joint Monitoring Programme for Water Supply, Sanitation and Hygiene public database to estimate population exposure to different WASH service levels. WASH-attributable undernutrition was estimated by combining the population attributable fractions (PAF) of diarrhoea caused by unsafe WASH and the PAF of undernutrition caused by diarrhoea. Soil-transmitted helminthiasis was fully attributed to unsafe WASH. FINDINGS: We estimate that 1·4 (95% CI 1·3-1·5) million deaths and 74 (68-80) million disability-adjusted life-years (DALYs) could have been prevented by safe WASH in 2019 across the four designated outcomes, representing 2·5% of global deaths and 2·9% of global DALYs from all causes. The proportion of diarrhoea that is attributable to unsafe WASH is 0·69 (0·65-0·72), 0·14 (0·13-0·17) for acute respiratory infections, and 0·10 (0·09-0·10) for undernutrition, and we assume that the entire disease burden from soil-transmitted helminthiasis was attributable to unsafe WASH. INTERPRETATION: WASH-attributable burden of disease estimates based on the levels of service established under the SDG framework show that progress towards the internationally agreed goal of safely managed WASH services for all would yield major public-health returns. FUNDING: WHO and Foreign, Commonwealth & Development Office.

Developmental biomechanics and age polyethism in leaf-cutter ants.

Many social insects display age polyethism: young workers stay inside the nest, and only older workers forage. This behavioural transition is accompanied by genetic and physiological changes, but the mechanistic origin of it remains unclear. To investigate if the mechanical demands on the musculoskeletal system effectively prevent young workers from foraging, we studied the biomechanical development of the bite apparatus in Atta vollenweideri leaf-cutter ants. Fully matured foragers generated peak in vivo bite forces of around 100 mN, more than one order of magnitude in excess of those measured for freshly eclosed callows of the same size. This change in bite force was accompanied by a sixfold increase in the volume of the mandible closer muscle, and by a substantial increase of the flexural rigidity of the head capsule, driven by a significant increase in both average thickness and indentation modulus of the head capsule cuticle. Consequently, callows lack the muscle force capacity required for leaf-cutting, and their head capsule is so compliant that large muscle forces would be likely to cause damaging deformations. On the basis of these results, we speculate that continued biomechanical development post eclosion may be a key factor underlying age polyethism, wherever foraging is associated with substantial mechanical demands.

Towards using a multi-material, pellet-fed additive manufacturing platform to fabricate novel imaging phantoms.

The design freedom afforded by additive manufacturing (AM) is now being leveraged across multiple applications, including many in the fields of imaging for personalised medicine. This study utilises a pellet-fed, multi-material AM machine as a route to fabricating new imaging phantoms, used for developing and refining algorithms for the detection of subtle soft tissue anomalies. Traditionally comprising homogeneous materials, higher-resolution scanning now allows for heterogeneous, multi-material phantoms. Polylactic acid (PLA), a thermoplastic urethane (TPU) and a thermoplastic elastomer (TPE) were investigated as potential materials. Manufacturing accuracy and precision were assessed relative to the digital design file, whilst the potential to achieve structural heterogeneity was evaluated by quantifying infill density via micro-computed tomography. Hounsfield units (HU) were also captured via a clinical scanner. The PLA builds were consistently too small, by 0.2 - 0.3%. Conversely, TPE parts were consistently larger than the digital file, though by only 0.1%. The TPU components had negligible differences relative to the specified sizes. The accuracy and precision of material infill were inferior, with PLA exhibiting greater and lower densities relative to the digital file, across the 3 builds. Both TPU and TPE produced infills that were too dense. The PLA material produced repeatable HU values, with poorer precision across TPU and TPE. All HU values tended towards, and some exceeded, the reference value for water (0 HU) with increasing infill density. These data have demonstrated that pellet-fed AM can produce accurate and precise structures, with the potential to include multiple materials providing an opportunity for more realistic and advanced phantom designs. In doing so, this will enable clinical scientists to develop more sensitive applications aimed at detecting ever more subtle variations in tissue, confident that their calibration models reflect their intended designs.

Time-restricted eating improves measures of daily glycaemic control in people with type 2 diabetes.

AIMS: Examine the effect of 5 d/wk, 9-h time-restricted eating (TRE) protocol on 24-h glycaemic control in adults with type 2 diabetes (T2D). METHODS: Nineteen adults with T2D (10 F/9 M; 50 ± 9 y, HbA1c 7.6% (60 mmol/mol), BMI ∼34 kg/m2) completed a pre-post non-randomised trial comprising of a 2-wk Habitual monitoring period followed by 9-h (10:00-19:00 h) TRE for 4-wk. Glycaemic control was assessed via continuous glucose monitoring (CGM; for mean 24-h glucose concentrations, 24-h total area under the curve (AUC) and glucose variability metrics), with dietary records and physical activity monitoring. Changes in CGM measures, dietary intake and physical activity were assessed with linear mixed-effects models. RESULTS: TRE did not alter dietary energy intake, macronutrient composition or physical activity, but reduced the daily eating window (-2 h 35 min, P < 0.001). Compared to the Habitual period, 24-h glucose concentrations (mean, SD) and AUC decreased in the 4-wk TRE period (mean: -0.7 ± 1.2 mmol/L, P = 0.02; SD: -0.2 ± 0.3 mmol/L, P = 0.01; 24-h AUC: -0.9 ± 1.4 mmol/L⋅h-1 P = 0.01). During TRE, participants spent 10% more time in range (3.9-10.0 mmol/L; P = 0.02) and 10% less time above range (>10.0 mmol/L; P = 0.02). CONCLUSIONS: Adhering 5 d/wk. to 9-h TRE improved glycaemic control in adults with T2D, independent of changes in physical activity or dietary intake. CLINICAL TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry, ACTRN12618000938202.

Trajectory of knee health in runners with and without heightened osteoarthritis risk: the TRAIL prospective cohort study protocol.

INTRODUCTION: Running is one of the most popular recreational activities worldwide, due to its low cost and accessibility. However, little is known about the impact of running on knee joint health in runners with and without a history of knee surgery. The primary aim of this longitudinal cohort study is to compare knee joint structural features on MRI and knee symptoms at baseline and 4-year follow-up in runners with and without a history of knee surgery. Secondary aims are to explore the relationships between training load exposures (volume and/or intensity) and changes in knee joint structure and symptoms over 4 years; explore the relationship between baseline running biomechanics, and changes in knee joint structure and symptoms over 4 years. In addition, we will explore whether additional variables confound, modify or mediate these associations, including sex, baseline lower-limb functional performance, knee muscle strength, psychological and sociodemographic factors. METHODS AND ANALYSIS: A convenience sample of at least 200 runners (sex/gender balanced) with (n=100) and without (n=100) a history of knee surgery will be recruited. Primary outcomes will be knee joint health (MRI) and knee symptoms (baseline; 4 years). Exposure variables for secondary outcomes include training load exposure, obtained daily throughout the study from wearable devices and three-dimensional running biomechanics (baseline). Additional variables include lower limb functional performance, knee extensor and flexor muscle strength, biomarkers, psychological and sociodemographic factors (baseline). Knowledge and beliefs about osteoarthritis will be obtained through predefined questions and semi-structured interviews with a subset of participants. Multivariable logistic and linear regression models, adjusting for potential confounding factors, will explore changes in knee joint structural features and symptoms, and the influence of potential modifiers and mediators. ETHICS AND DISSEMINATION: Approved by the La Trobe University Ethics Committee (HEC-19524). Findings will be disseminated to stakeholders, peer-review journals and conferences.

A biomechanical model for the relation between bite force and mandibular opening angle in arthropods.

Bite forces play a key role in animal ecology: they affect mating behaviour, fighting success, and the ability to feed. Although feeding habits of arthropods have a significant ecological and economical impact, we lack fundamental knowledge on how the morphology and physiology of their bite apparatus controls bite performance, and its variation with mandible gape. To address this gap, we derived a biomechanical model that characterizes the relationship between bite force and mandibular opening angle from first principles. We validate this model by comparing its geometric predictions with morphological measurements on the muscoloskeletal bite apparatus of Atta cephalotes leaf-cutter ants, using computed tomography (CT) scans obtained at different mandible opening angles. We then demonstrate its deductive and inductive utility with three examplary use cases: Firstly, we extract the physiological properties of the leaf-cutter ant mandible closer muscle from in vivo bite force measurements. Secondly, we show that leaf-cutter ants are specialized to generate extraordinarily large bite forces, equivalent to about 2600 times their body weight. Thirdly, we discuss the relative importance of morphology and physiology in determining the magnitude and variation of bite force. We hope that a more detailed quantitative understanding of the link between morphology, physiology, and bite performance will facilitate future comparative studies on the insect bite apparatus, and help to advance our knowledge of the behaviour, ecology and evolution of arthropods.

Interleukin-11 receptor subunit α-1 is required for maximal airway responsiveness to methacholine after acute exposure to ozone.

Interleukin (IL)-11, a multifunctional cytokine, contributes to numerous biological processes, including adipogenesis, hematopoiesis, and inflammation. Asthma, a respiratory disease, is notably characterized by reversible airway obstruction, persistent lung inflammation, and airway hyperresponsiveness (AHR). Nasal insufflation of IL-11 causes AHR in wild-type mice while lung inflammation induced by antigen sensitization and challenge, which mimics features of atopic asthma in humans, is attenuated in mice genetically deficient in IL-11 receptor subunit α-1 (IL-11Rα1-deficient mice), a transmembrane receptor that is required conjointly with glycoprotein 130 to transduce IL-11 signaling. Nevertheless, the contribution of IL-11Rα1 to characteristics of nonatopic asthma is unknown. Thus, based on the aforementioned observations, we hypothesized that genetic deficiency of IL-11Rα1 attenuates lung inflammation and increases airway responsiveness after acute inhalation exposure to ozone (O3), a criteria pollutant and nonatopic asthma stimulus. Accordingly, 4 and/or 24 h after cessation of exposure to filtered room air or O3, we assessed lung inflammation and airway responsiveness in wild-type and IL-11Rα1-deficient mice. With the exception of bronchoalveolar lavage macrophages and adiponectin, which were significantly increased and decreased, respectively, in O3-exposed IL-11Rα1-deficient as compared with O3-exposed wild-type mice, no other genotype-related differences in lung inflammation indices that we quantified were observed in O3-exposed mice. However, airway responsiveness to acetyl-ß-methylcholine chloride (methacholine) was significantly diminished in IL-11Rα1-deficient as compared with wild-type mice after O3 exposure. In conclusion, these results demonstrate that IL-11Rα1 minimally contributes to lung inflammation but is required for maximal airway responsiveness to methacholine in a mouse model of nonatopic asthma.

Assessment of Retinal Changes Following Intravitreal Aflibercept in 2 Patients With Von Hippel-Lindau Disease-Related Retinal Capillary Hemangioblastoma.

This case report of 2 patients describes peripheral Von Hippel-Lindau disease associated with a series of aflibercept injections.